Influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on the requirement of carbamazepine maintenance dose in persons with epilepsy (PWE) of Southern part of India: a cross-sectional genetic association study

Shravan Venkatraman; Kesavan Ramasamy; Pradeep P. Nair; Priyadharsini Rajendran

doi:10.1515/dmpt-2022-0157

Article

Influence of EPHX1 c.337 T>C and UGT2B72* genetic polymorphisms on the requirement of carbamazepine maintenance dose in persons with epilepsy (PWE) of Southern part of India: a cross-sectional genetic association study

Shravan Venkatraman , Kesavan Ramasamy , Pradeep P. Nair and Priyadharsini Rajendran

Published/Copyright: March 1, 2023

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From the journal Drug Metabolism and Personalized Therapy Volume 38 Issue 2

Abstract

Objectives

Carbamazepine (CBZ) is a first-line antiseizure drug used for focal onset seizures. It exhibits inter-individual variability in plasma carbamazepine levels and there are both genetic and non-genetic factors having a role in the requirement of CBZ maintenance dose. The aim was to study the influence of EPHX1 c.337 T>C and UGT2B7*2 genetic polymorphisms on CBZ maintenance dose requirement in persons with epilepsy.

Methods

Persons with epilepsy (PWE) of both gender of age 15–65 years on carbamazepine monotherapy who had been taking same maintenance dose for one year were eligible. Five milliliter of venous blood was collected in 10% EDTA under aseptic precautions. After centrifugation, the cellular component was used for DNA extraction and genotyping. For three genotypes of EPHX1 c.337 T>C and UGT2B7*2, the differences in mean carbamazepine dose were analyzed using Analysis of Variance (ANOVA). An unpaired t-test was used to draw a comparison between the genotypes and CBZ maintenance dose requirement for dominant and recessive models of EPHX1 c.337 T>C and UGT2B7*2. A value of p<0.05 was considered to be statistically significant.

Results

For UGT2B7*2 (rs 7439366), CT required a higher dose (CT 626 mg/day and TT 523 mg/day) but not found to be significant (p-value 0.167). PWE carrying CT genotype of EPHX1 c.337 T>C had 62 mg higher dose when compared to homozygous mutant CC (590 mg/day for CT and 528 mg/day for CC) but p-value was not found to be significant (p-value 0.835).

Conclusions

The results of our study done in 115 PWE showed there was a lack of association between SNPs of EPHX1 c.337 T>C, UGT2B7*2 and CBZ maintenance dose requirement in Southern part of India and this finding has to be confirmed in a larger sample size.

Keywords: carbamazepine; EPHX1 ; maintenance dose; UGT2B7*2

Corresponding author: Dr. Kesavan Ramasamy, Associate Professor, Department of Pharmacology, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Institute Block, III Floor, Puducherry, India, Phone: 0413 2272380, E-mail: kes7ramasamy@gmail.com

Funding source: Intramural Funding, JIPMER

Award Identifier / Grant number: JIP/DEAN(R)/INTRAMURAL/PHS 1/2019-20 [Dt 10/9/2019]

Acknowledgments

We would like to thank our patients for their support in completing the study. We would also extend our thanks to Lavanya Narayanan for her sincere help.

Research funding: Funded by Intramural Funding, JIPMER (grant number JIP/DEAN(R)/INTRAMURAL/PHS 1/2019-20 [Dt 10/9/2019]).
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
Competing interests: Authors state no conflict of interest.
Informed consent: Informed consent was obtained from all individuals included in this study.
Ethical approval: We got the approval of the Institutional Ethics Committee for observational studies (JIP/IEC/2019/193).

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Received: 2022-08-09

Accepted: 2022-12-12

Published Online: 2023-03-01

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Articles in the same Issue

https://doi.org/10.1515/dmpt-2022-0157

Keywords for this article

carbamazepine; EPHX1; maintenance dose; UGT2B7*2